Sophie E. T. Kendall-Price, Ryan J. O. Nichol, Andrea Taladriz-Sender, Ryan Phelps, Partha Malakar, Gregory M. Greetham, Glenn A. Burley* and Neil T. Hunt*,
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Long-Range Allosteric Modulation of DNA Duplex Dynamics Induced by Pyrrole-Imidazole Polyamide Binding
The allosteric modulation of the structural dynamics of double-stranded DNA (dsDNA) duplexes as a function of distance from the site of a minor groove binding ligand is reported. Time-resolved temperature-jump infrared spectroscopy is used to interrogate the impact of binding a pyrrole-imidazole polyamide to dsDNA sequences 8–14 base-pairs in length. Our results demonstrate that the binding of the hairpin polyamide to its target site (5′-WWGTACW-3′; W = A/T) causes a marked suppression of structural dynamics, such as end fraying, with suppression observed in both the 3′ and 5′ directions. Quantitative analysis of end fraying suppression reveals a propagation length for dynamic modulation of 30 base-pairs. Identifying the structural impact of minor groove binding to dsDNA sequences furthers our understanding of the influence of dsDNA recognition and informs the design of next-generation synthetic transcription factors.
期刊介绍：
The Journal of Physical Chemistry (JPC) Letters is devoted to reporting new and original experimental and theoretical basic research of interest to physical chemists, biophysical chemists, chemical physicists, physicists, material scientists, and engineers. An important criterion for acceptance is that the paper reports a significant scientific advance and/or physical insight such that rapid publication is essential. Two issues of JPC Letters are published each month.
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